4BLB

Crystal structure of a human Suppressor of fused (SUFU)-GLI1p complex

Summary for 4BLB

• Entry DOI: 10.2210/pdb4blb/pdb
• Related: 4BL8 4BL9 4BLA 4BLD
• Related PRD ID: PRD_900001
• Descriptor: MALTOSE-BINDING PERIPLASMIC PROTEIN, SUPPRESSOR OF FUSED HOMOLOG, ZINC FINGER PROTEIN GLI1, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: sugar binding protein-signaling protein complex, signaling protein, chimera, fusion protein, hedgehog signaling, gene regulation, transcription factor
• Biological source: ESCHERICHIA COLI; More
• Total number of polymer chains: 8
• Total formula weight: 342766.60

Authors

Cherry, A.L.,Finta, C.,Karlstrom, M.,De Sanctis, D.,Toftgard, R.,Jovine, L. (deposition date: 2013-05-02, release date: 2013-11-27, Last modification date: 2024-05-08)

Primary citation

Cherry, A.L.,Finta, C.,Karlstrom, M.,Jin, Q.,Schwend, T.,Astorga-Wells, J.,Zubarev, R.A.,Del Campo, M.,Criswell, A.R.,De Sanctis, D.,Jovine, L.,Toftgard, R.
Structural Basis of Sufu-GLI Interaction in Hedgehog Signalling Regulation
Acta Crystallogr.,Sect.D, 69:2579-, 2013

PubMed Abstract: Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU-GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU-GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics.

PubMed: 24311597
DOI: 10.1107/S0907444913028473

Experimental method

X-RAY DIFFRACTION (2.8 Å)